JPH02121928A - Nutritive infusion solution composition containing dipeptide of l-tyrosine - Google Patents
Nutritive infusion solution composition containing dipeptide of l-tyrosineInfo
- Publication number
- JPH02121928A JPH02121928A JP63273826A JP27382688A JPH02121928A JP H02121928 A JPH02121928 A JP H02121928A JP 63273826 A JP63273826 A JP 63273826A JP 27382688 A JP27382688 A JP 27382688A JP H02121928 A JPH02121928 A JP H02121928A
- Authority
- JP
- Japan
- Prior art keywords
- tyr
- amino acid
- tyrosine
- dipeptide
- infusion
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 title claims abstract description 54
- 239000000203 mixture Substances 0.000 title claims abstract description 36
- 108010016626 Dipeptides Proteins 0.000 title claims abstract description 27
- 239000003978 infusion fluid Substances 0.000 title abstract description 9
- 230000000050 nutritive effect Effects 0.000 title abstract 4
- 229940024606 amino acid Drugs 0.000 claims abstract description 46
- 150000001413 amino acids Chemical class 0.000 claims abstract description 45
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 claims abstract description 23
- 239000003797 essential amino acid Substances 0.000 claims abstract description 13
- 235000020776 essential amino acid Nutrition 0.000 claims abstract description 13
- 229960004441 tyrosine Drugs 0.000 claims abstract description 12
- 229960005190 phenylalanine Drugs 0.000 claims abstract description 5
- 125000003798 L-tyrosyl group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C([H])([H])C1=C([H])C([H])=C(O[H])C([H])=C1[H] 0.000 claims abstract 3
- 238000001802 infusion Methods 0.000 claims description 33
- 235000016709 nutrition Nutrition 0.000 claims description 17
- 239000000126 substance Substances 0.000 claims 1
- 230000001575 pathological effect Effects 0.000 abstract description 9
- 201000010099 disease Diseases 0.000 abstract description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 6
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 abstract description 5
- WCRFXRIWBFRZBR-GGVZMXCHSA-N Thr-Tyr Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 WCRFXRIWBFRZBR-GGVZMXCHSA-N 0.000 abstract description 2
- 238000013329 compounding Methods 0.000 abstract description 2
- HPYDSVWYXXKHRD-VIFPVBQESA-N Tyr-Gly Chemical compound [O-]C(=O)CNC(=O)[C@@H]([NH3+])CC1=CC=C(O)C=C1 HPYDSVWYXXKHRD-VIFPVBQESA-N 0.000 abstract 1
- 238000004090 dissolution Methods 0.000 abstract 1
- 230000001747 exhibiting effect Effects 0.000 abstract 1
- 235000001014 amino acid Nutrition 0.000 description 41
- 238000012360 testing method Methods 0.000 description 11
- 230000000694 effects Effects 0.000 description 10
- 238000009472 formulation Methods 0.000 description 5
- 238000001990 intravenous administration Methods 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 5
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- 125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 4
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 3
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 3
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 3
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 3
- LHSGPCFBGJHPCY-STQMWFEESA-N Leu-Tyr Chemical compound CC(C)C[C@H](N)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 LHSGPCFBGJHPCY-STQMWFEESA-N 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 210000003734 kidney Anatomy 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 206010002091 Anaesthesia Diseases 0.000 description 2
- 208000037157 Azotemia Diseases 0.000 description 2
- 208000031648 Body Weight Changes Diseases 0.000 description 2
- QNAYBMKLOCPYGJ-UHFFFAOYSA-N D-alpha-Ala Natural products CC([NH3+])C([O-])=O QNAYBMKLOCPYGJ-UHFFFAOYSA-N 0.000 description 2
- 239000004471 Glycine Substances 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- QNAYBMKLOCPYGJ-UWTATZPHSA-N L-Alanine Natural products C[C@@H](N)C(O)=O QNAYBMKLOCPYGJ-UWTATZPHSA-N 0.000 description 2
- AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 description 2
- ODKSFYDXXFIFQN-BYPYZUCNSA-N L-arginine Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N ODKSFYDXXFIFQN-BYPYZUCNSA-N 0.000 description 2
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 2
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 2
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 2
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 2
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- NLKUJNGEGZDXGO-XVKPBYJWSA-N Tyr-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 NLKUJNGEGZDXGO-XVKPBYJWSA-N 0.000 description 2
- PDSLRCZINIDLMU-QWRGUYRKSA-N Tyr-Glu Chemical compound OC(=O)CC[C@@H](C(O)=O)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 PDSLRCZINIDLMU-QWRGUYRKSA-N 0.000 description 2
- AUEJLPRZGVVDNU-STQMWFEESA-N Tyr-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 AUEJLPRZGVVDNU-STQMWFEESA-N 0.000 description 2
- MFEVVAXTBZELLL-GGVZMXCHSA-N Tyr-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 MFEVVAXTBZELLL-GGVZMXCHSA-N 0.000 description 2
- OYOQKMOWUDVWCR-RYUDHWBXSA-N Tyr-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OYOQKMOWUDVWCR-RYUDHWBXSA-N 0.000 description 2
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Chemical compound CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 2
- 229960003767 alanine Drugs 0.000 description 2
- 230000037005 anaesthesia Effects 0.000 description 2
- 230000004579 body weight change Effects 0.000 description 2
- 230000007812 deficiency Effects 0.000 description 2
- 239000003792 electrolyte Substances 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 108010012058 leucyltyrosine Proteins 0.000 description 2
- 208000019423 liver disease Diseases 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- 230000002028 premature Effects 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- 108090000765 processed proteins & peptides Proteins 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 229920002379 silicone rubber Polymers 0.000 description 2
- 239000004945 silicone rubber Substances 0.000 description 2
- 235000000346 sugar Nutrition 0.000 description 2
- 150000008163 sugars Chemical group 0.000 description 2
- XOAAWQZATWQOTB-UHFFFAOYSA-N taurine Chemical compound NCCS(O)(=O)=O XOAAWQZATWQOTB-UHFFFAOYSA-N 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 239000011573 trace mineral Substances 0.000 description 2
- 235000013619 trace mineral Nutrition 0.000 description 2
- 208000009852 uremia Diseases 0.000 description 2
- 210000002620 vena cava superior Anatomy 0.000 description 2
- 235000013343 vitamin Nutrition 0.000 description 2
- 239000011782 vitamin Substances 0.000 description 2
- 229940088594 vitamin Drugs 0.000 description 2
- 229930003231 vitamin Natural products 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 238000005303 weighing Methods 0.000 description 2
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 description 1
- ALZVPLKYDKJKQU-XVKPBYJWSA-N Ala-Tyr Chemical compound C[C@H](N)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 ALZVPLKYDKJKQU-XVKPBYJWSA-N 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- XBGGUPMXALFZOT-VIFPVBQESA-N Gly-Tyr Chemical compound NCC(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 XBGGUPMXALFZOT-VIFPVBQESA-N 0.000 description 1
- MUFXDFWAJSPHIQ-XDTLVQLUSA-N Ile-Tyr Chemical compound CC[C@H](C)[C@H]([NH3+])C(=O)N[C@H](C([O-])=O)CC1=CC=C(O)C=C1 MUFXDFWAJSPHIQ-XDTLVQLUSA-N 0.000 description 1
- FFEARJCKVFRZRR-UHFFFAOYSA-N L-Methionine Natural products CSCCC(N)C(O)=O FFEARJCKVFRZRR-UHFFFAOYSA-N 0.000 description 1
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- 229930064664 L-arginine Natural products 0.000 description 1
- 235000014852 L-arginine Nutrition 0.000 description 1
- LEVWYRKDKASIDU-IMJSIDKUSA-N L-cystine Chemical compound [O-]C(=O)[C@@H]([NH3+])CSSC[C@H]([NH3+])C([O-])=O LEVWYRKDKASIDU-IMJSIDKUSA-N 0.000 description 1
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 1
- 229930182844 L-isoleucine Natural products 0.000 description 1
- 239000004395 L-leucine Substances 0.000 description 1
- 235000019454 L-leucine Nutrition 0.000 description 1
- LHSGPCFBGJHPCY-UHFFFAOYSA-N L-leucine-L-tyrosine Natural products CC(C)CC(N)C(=O)NC(C(O)=O)CC1=CC=C(O)C=C1 LHSGPCFBGJHPCY-UHFFFAOYSA-N 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- 229930195722 L-methionine Natural products 0.000 description 1
- 229930182821 L-proline Natural products 0.000 description 1
- JXNRXNCCROJZFB-RYUDHWBXSA-O L-tyrosiniumyl-L-arginine(1+) Chemical compound NC(=[NH2+])NCCC[C@@H](C([O-])=O)NC(=O)[C@@H]([NH3+])CC1=CC=C(O)C=C1 JXNRXNCCROJZFB-RYUDHWBXSA-O 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- 102000008109 Mixed Function Oxygenases Human genes 0.000 description 1
- 108010074633 Mixed Function Oxygenases Proteins 0.000 description 1
- 206010060860 Neurological symptom Diseases 0.000 description 1
- 108010038807 Oligopeptides Proteins 0.000 description 1
- 102000015636 Oligopeptides Human genes 0.000 description 1
- AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 description 1
- 239000004473 Threonine Substances 0.000 description 1
- QJKMCQRFHJRIPU-XDTLVQLUSA-N Tyr-Ile Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 QJKMCQRFHJRIPU-XDTLVQLUSA-N 0.000 description 1
- AOLHUMAVONBBEZ-STQMWFEESA-N Tyr-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 AOLHUMAVONBBEZ-STQMWFEESA-N 0.000 description 1
- VEYJKJORLPYVLO-RYUDHWBXSA-N Val-Tyr Chemical compound CC(C)[C@H](N)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 VEYJKJORLPYVLO-RYUDHWBXSA-N 0.000 description 1
- PNNCWTXUWKENPE-UHFFFAOYSA-N [N].NC(N)=O Chemical compound [N].NC(N)=O PNNCWTXUWKENPE-UHFFFAOYSA-N 0.000 description 1
- 159000000021 acetate salts Chemical class 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 239000004469 amino acid formulation Substances 0.000 description 1
- 230000037354 amino acid metabolism Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 229960001230 asparagine Drugs 0.000 description 1
- 229960005261 aspartic acid Drugs 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 150000003943 catecholamines Chemical class 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 229960003067 cystine Drugs 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 235000013601 eggs Nutrition 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 229960002989 glutamic acid Drugs 0.000 description 1
- 108010087823 glycyltyrosine Proteins 0.000 description 1
- 229960002885 histidine Drugs 0.000 description 1
- 235000020256 human milk Nutrition 0.000 description 1
- 210000004251 human milk Anatomy 0.000 description 1
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- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 229960000310 isoleucine Drugs 0.000 description 1
- 208000017169 kidney disease Diseases 0.000 description 1
- 108010053037 kyotorphin Proteins 0.000 description 1
- 150000003893 lactate salts Chemical class 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 229960003136 leucine Drugs 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
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- 229960004452 methionine Drugs 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 235000003715 nutritional status Nutrition 0.000 description 1
- -1 organic acid salts Chemical class 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 229960003104 ornithine Drugs 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
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- 238000003786 synthesis reaction Methods 0.000 description 1
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Abstract
Description
【発明の詳細な説明】
〔産業上の利用分野〕
本発明は、栄養輸液組成物、さらに詳しくはＬ−チロシ
ンのジペプチドを含有するアミノ酸栄養輸液輸液組成物
に関する。DETAILED DESCRIPTION OF THE INVENTION [Industrial Field of Application] The present invention relates to a nutritional infusion composition, and more particularly to an amino acid nutritional infusion infusion composition containing a dipeptide of L-tyrosine.
（従来の技術）
経静脈用アミノ酸輸液は、各種疾患時あるいは術前術後
などにおいて、アミノ酸若しくは蛋白質を摂取する必要
があるにもかかわらず、経口的に摂取できないか又は摂
取量が不十分な場合の栄養補給を目的として広く利用さ
れている。(Prior art) Intravenous amino acid infusions are used when amino acids or proteins need to be ingested during various diseases or pre- and post-operatively, but cannot be taken orally or the intake is insufficient. It is widely used for nutritional supplementation purposes.
最近、病態でのアミノ酸代謝に関する研究が進んだこと
により、種々のアミノ酸の病態での役割が明らかになっ
たことから、アミノ酸輸液の開発の流れは治療面を重視
した病態別アミノ酸輸液の開発と各種病態に比較的共通
している栄養学的特徴を是正しようとする汎用性の高い
アミノ酸輸液開発の二つの方向に分かれている。Recently, research on amino acid metabolism in pathological conditions has progressed, and the role of various amino acids in pathological conditions has become clear.The development of amino acid infusions has shifted to the development of amino acid infusions for each condition with an emphasis on treatment. The research is divided into two directions: the development of highly versatile amino acid infusions that attempt to correct nutritional characteristics that are relatively common to various pathological conditions.
アミノ酸輸液に使用されているアミノ酸のなかでもＬ−
チロシン（Ｔｙｒ）は、肝臓病、尿毒症、未熟児、新生
児などでその必要性が示されている。Among the amino acids used in amino acid infusions, L-
Tyrosine (Tyr) has been shown to be necessary for liver diseases, uremia, premature infants, newborns, and the like.
なかでも、尿毒ｇ患者では、特にＴｙｒが低値を示して
いる。これは、し−フェニルアラニン（Ｐｈｅ）水酸化
酵素の活性が低いため、ＰｈｅからＴｙｒの生成が不充
分なことによっている。Ｔｙｒ欠乏によるタンパク合成
の減少は、患者の栄養状態を極度に低下させることが認
められている。さらにＴｙｒがカテコールアミンの前駆
体であることから、これが不足すると種々の神経症状を
引き起こす可能性も指摘されており、それらの患者にお
いてＴｙｒは必要なアミノ酸としての位置付けがなされ
つつある。そのそのため病態に適したようにＴｙｒを処
方化したアミノ酸輸液が望まれているのが現状である。Among these, Tyr has a particularly low value in uremic G patients. This is due to insufficient production of Tyr from Phe due to low activity of phenylalanine (Phe) hydroxylase. It has been recognized that decreased protein synthesis due to Tyr deficiency severely reduces the nutritional status of patients. Furthermore, since Tyr is a precursor of catecholamines, it has been pointed out that a deficiency thereof may cause various neurological symptoms, and Tyr is being positioned as an essential amino acid in these patients. Therefore, there is currently a demand for an amino acid infusion containing Tyr in a formulation suitable for the disease state.
しかしながら、Ｔｙｒの水に対する溶解度は、２５°Ｃ
で０．０４５ ｇ／ａにすぎず輸液の成分として必要量
を任意に処方化することが困難である。However, the solubility of Tyr in water is 25°C.
It is only 0.045 g/a, making it difficult to formulate the necessary amount as an infusion component.
Ｔｙｒの輸液中における処方に関しては、従来、１９５
７年ＦＡＯ特別委員会報告に基づく人乳または全卵のア
ミノ酸組成によるもの等、健康人の栄養処方に基づく組
成が用いられている。しかしながら、先に述べたように
健康人にあってはＴｙｒはＰｈｅから充分量合成される
が、ある種の病態では、そのような合成が不充分であり
、Ｔｙｒは必要なアミノ酸として位置づけられている。Regarding the prescription of Tyr in infusion, conventionally, 195
Compositions based on nutritional prescriptions for healthy people are used, such as those based on the amino acid composition of human milk or whole eggs based on the 2007 FAO Special Committee Report. However, as mentioned earlier, Tyr is synthesized in sufficient amounts from Phe in healthy people, but in certain pathological conditions, such synthesis is insufficient, and Tyr is positioned as an essential amino acid. There is.
そのため健康人の栄養処方と異なることは明らかである
。Therefore, it is clear that the nutritional prescription is different from that of a healthy person.
そのことを考慮した病態時の処方に関しては、すでに特
開昭５９−１６１８７に開示されている。Prescriptions for pathological conditions that take this into consideration have already been disclosed in Japanese Patent Application Laid-Open No. 16187/1983.
この公報によれば、ＴｙｒはＰｈｅの１ ／１２〜１／
１７の範囲で、かつ０．４５ｇ〜０．５５ｇ／ｌの濃度
で含有することが好結果を生むと示されている。According to this publication, Tyr is 1/12 to 1/1/1 of Phe.
17 and concentrations of 0.45 g/l to 0.55 g/l have been shown to produce good results.
しかしながら、摂取された必須アミノ酸Ｐｈｅの生体内
での代謝研究によると、摂取Ｐｈｅの５０％〜７０％が
Ｔｙｒに変換されることが見出されている。However, according to in vivo metabolic studies of ingested essential amino acid Phe, it has been found that 50% to 70% of ingested Phe is converted to Tyr.
−船釣なアミノ酸輸液中にＰｈｅは５．０〜１０．０ｇ
／ｌの濃度が必要であるとされている。先はどの変換率
から考えて、単純に計算しても、病態時にはＰｈｅの処
方のうち２．５〜７．０ｇ／ １分をＴｙｒで置き換え
る必要のあることが推測できる。このことを考えると、
特開昭５９−１６１８７で示された処方は、Ｔｙｒの溶
解度の範囲内で考えたもので、十分病態時を考慮したも
のと言い難い。しかるに、従来そのように高濃度のＴｙ
ｒを含有したアミノ酸輸液は知られていない。-Phe is 5.0-10.0g in amino acid infusion
It is said that a concentration of /l is required. Based on the conversion rate and simple calculations, it can be inferred that 2.5 to 7.0 g/min of the Phe prescription needs to be replaced with Tyr during pathological conditions. Considering this,
The formulation shown in JP-A-59-16187 was designed within the solubility of Tyr, and it cannot be said that it sufficiently takes into account the disease state. However, conventionally, such high concentrations of Ty
There are no known amino acid infusions containing r.
ところで、Ｔｙｒの濃度を高める方法については既にい
くつかｇ：Ｅ案されている。特開昭５６−８３１２には
、Ｌ−アラニル−し−チロノン、Ｌ−アルギニル−し−
チロシン、Ｌ−チロシル−Ｌ−アルギニンなどのペプチ
ドを用いる方法。特開昭６１２４７３５４には、グリシ
ル−Ｌ−チロシン、Ｌ−アラニル−し−チロシンが、特
開昭６２１５１１５６にはＬ−アスパラチル−Ｌ−チロ
シンが開示されている。しかしながら、いづれにしても
Ｔｙｒの処方について詳細に検討したものとは言い難い
。By the way, several g:E methods have already been proposed for increasing the concentration of Tyr. JP-A-56-8312 discloses L-alanyl-thironone, L-arginyl-thironone,
A method using peptides such as tyrosine and L-tyrosyl-L-arginine. JP-A-61247354 discloses glycyl-L-tyrosine and L-alanyl-tyrosine, and JP-A-62151156 discloses L-asparatyl-L-tyrosine. However, in any case, it cannot be said that the prescription of Tyr was studied in detail.
本発明の課題は、溶解度の低いチロシンを製剤学的制約
を受けずに目的に合った比率で必要な量含有し、かつ各
種の目的とする疾患時に優れた栄養効果を発揮させる新
しい処方のアミノ酸栄養輸液組成物を提供することであ
る。The object of the present invention is to create a new amino acid formulation that contains tyrosine, which has low solubility, in the required amount in a proportion suitable for the purpose without being subject to pharmaceutical restrictions, and that exhibits excellent nutritional effects in the treatment of various target diseases. An object of the present invention is to provide a nutritional infusion composition.
本発明者らは、上記課題を解決するために種々検討した
結果、製剤学的問題であるＴｙｒの溶解度は、Ｔｙｒの
ジペプチドを用いることにより解決でき、さらにＴｙｒ
の効果を得るためには、アミノ酸輸液中でのＴｙｒの濃
度に至適範囲があり、その至適範囲は、同時に配合され
る他のアミノＦｌｉ濃度と相関のあることを見出し、本
発明を完成することができた。As a result of various studies to solve the above problems, the present inventors found that the pharmaceutical problem of solubility of Tyr can be solved by using a dipeptide of Tyr, and that
In order to obtain this effect, there is an optimal range for the concentration of Tyr in an amino acid infusion, and we have discovered that this optimal range is correlated with the concentration of other amino acids that are mixed at the same time, and completed the present invention. We were able to.
既に述べたようにＴｙｒについては、ある種の病態にと
っては必要なアミノ酸であることが見出されており、実
用上高濃度化の必要性が望まれていた。しかしながら製
剤学的問題のため、他のアミノ酸との相関や濃度ついて
総合的に検討されておらず、高濃度化の処方が決定され
るまでには至っていなかった。Ｔｙｒはその前駆体であ
る必須アミノ酸Ｐｈｅから合成され、Ｐｈｅが最も相関
しているアミノ酸である。As mentioned above, Tyr has been found to be an essential amino acid for certain pathological conditions, and it has been desired for practical purposes to increase its concentration. However, due to pharmaceutical problems, the correlation with other amino acids and concentrations have not been comprehensively investigated, and a formulation with a high concentration has not yet been determined. Tyr is synthesized from its precursor, the essential amino acid Phe, with Phe being the most related amino acid.
本発明者らは、このような考察に基づいてＴｙｒとＰｈ
ｅの配合量、必須アミノ酸と非必須アミノ酸の配合量と
の間には特有の関係があるものと考え検討を行った。そ
の結果、肝臓病、尿毒症、未熟児、新生児などの病態時
に使用することのできるアミノ酸組成比を見出し本発明
を完成するに至った。Based on these considerations, the present inventors have determined that Tyr and Ph
We considered that there is a unique relationship between the amount of e and the amount of essential amino acids and non-essential amino acids. As a result, they discovered an amino acid composition ratio that can be used in pathological conditions such as liver disease, uremia, premature infants, and newborns, and completed the present invention.
すなわち、本発明は、必須アミノ酸、非必須アミノ酸及
びチロシン残基を含むジペプチドの少なくとも１種を配
合したアミノ酸栄Ｉ＠液組成物であって、該ジペプチド
をアミノ酸に換算した場合、少なくとも下記アミノ酸を
下記の組成範囲内で含有し、Ｐｈｅに対するＴｙｒの重
量比（↑ｙｒ／Ｐｈｅ）が０１１以上であり、Ｔｙｒの
濃度が０．６ｇ＃！以上であることを特徴とする組成物
を提供するものである。That is, the present invention provides an amino acid serum I@liquid composition containing at least one dipeptide containing an essential amino acid, a non-essential amino acid, and a tyrosine residue, which contains at least the following amino acids when the dipeptide is converted into an amino acid. Contains within the following composition range, the weight ratio of Tyr to Phe (↑yr/Phe) is 011 or more, and the concentration of Tyr is 0.6g#! The present invention provides a composition characterized by the above characteristics.
アミノ酸
組成範囲
輸／全アミノ酸１００ｇ）
Ｌ−イソロイシン（ｌｉｅ）
Ｌ−ロイシン（Ｌｅｕ）
し−リジン（Ｌｙｓ）
Ｌ−メチオニン（Ｎｅｔ）
５．０ 〜２０．０
５．０ 〜２０．０
３．０ 〜１５．０
１．０ 〜１０．０
Ｌ−フェニルアラニン（Ｐｈｅ）
Ｌ−スレオニン（Ｔｈｒ）
Ｌ−トリプトファン（Ｔｒｐ）
Ｌ−バリン（Ｖａｌ）
Ｌ−アラニン（Ａｌａ）
Ｌ−アルギニン（Ａｒｇ）
Ｌ−アスパラギンＭ（＾ｓｐ）
し−システィン（Ｃｙｓ）
Ｌ−グルタミン酸（Ｇｌｕ）
Ｌ−ヒスチジン（Ｈｉｓ）
Ｌ−プロリン（Ｐｒｏ）
Ｌ−セリン（Ｓｅｒ）
Ｌ−チロシン（Ｔｙｒ）
グリシン（Ｇｌｙ）
Ｌ−オルニチン（Ｏｒｎ）
タウリン（Ｔａｕ）
１．０ 〜１０．０
２．０ 〜１２．０
０．２５〜５．０
５、Ｏ〜 ２０．０
２．０ 〜１５．０
２．０ 〜１５，０
０〜４．０
０〜２．０
０〜８．０
０〜１０．０
０〜１０．０
０〜８．０
０．５ 〜１０．０
３．０ − １５．０
０〜５．０
０〜１５．０
前記の「該ジペプチドをアミノ酸に換算した場合」とは
［該ジペプチドの配合量を完全に加水分解したとき生成
する各アミノＮＩ量に換算したとき」を會味する。Amino acid composition range/total amino acids 100g) L-isoleucine (lie) L-leucine (Leu) Lysine (Lys) L-methionine (Net) 5.0 - 20.0 5.0 - 20.0 3.0 ~15.0 1.0 ~10.0 L-phenylalanine (Phe) L-threonine (Thr) L-tryptophan (Trp) L-valine (Val) L-alanine (Ala) L-arginine (Arg) L-asparagine M(^sp) Cystine (Cys) L-Glutamic acid (Glu) L-Histidine (His) L-Proline (Pro) L-Serine (Ser) L-Tyrosine (Tyr) Glycine (Gly) L-Ornithine (Orn ) Taurine (Tau) 1.0 ~ 10.0 2.0 ~ 12.0 0.25 ~ 5.0 5, O ~ 20.0 2.0 ~ 15.0 2.0 ~ 15,0 0 ~ 4 .0 0-2.0 0-8.0 0-10.0 0-10.0 0-8.0 0.5-10.0 3.0 - 15.0 0-5.0 0-15. 0 The above-mentioned "when the dipeptide is converted into an amino acid" refers to the case where the amount of the dipeptide is converted into the amount of each amino NI produced when the dipeptide is completely hydrolyzed.
本発明で用いるチロシン残基を含むジペプチドとして、
好ましくはＬ−スレオニル−Ｌ−チロシン（Ｔｈｒ−Ｔ
ｙｒ）、Ｌ−ロイシル−し−チロシン（ＬｅｕＴｙｒ）
、Ｌ−イソロイシル−Ｌ−チロシン（目ｅＴｙｒ）、
Ｌ−バリル−Ｌ−チロシン（Ｖａｔ−Ｔｙｒ）、し−チ
ロシル−グリシン（Ｔｙｒ−Ｇｌｙ）、し−チロシル−
Ｌ−アラニン（Ｔｙｒ−Ａｌａ） 、Ｌ−チロシル−し
−ロイシン（Ｔｙｒ−Ｌｅｕ） 、Ｌ−チロシル−Ｌ−
イソロイシン（Ｔｙｒ−１ｉｅ） 、Ｌ−チロシル−Ｌ
−バリン（Ｔｙｒ−Ｖａｌ）、し−チロシル−Ｌ−アス
パラギン酸（Ｔｙｒ−へｓｐ） 、Ｌ−チロシル−し−
リジン（Ｔｙｒ−Ｌｙｓ） 、Ｌ−チロシル−Ｌ−スレ
オニン（Ｔｙｒ−Ｔｈｒ）Ｌ−チロシル−Ｌ−グルタミ
ン酸（Ｔｙｒ−Ｇｔｕ）、し−チロンルーし一グルタミ
ン（Ｔｙｒ−Ｇｌｕ）が用いられる。As a dipeptide containing a tyrosine residue used in the present invention,
Preferably L-threonyl-L-tyrosine (Thr-T
yr), L-leucyl-tyrosine (LeuTyr)
, L-isoleucyl-L-tyrosine (order eTyr),
L-valyl-L-tyrosine (Vat-Tyr), Tyr-Glycine (Tyr-Gly), Tyr-Tyr-
L-alanine (Tyr-Ala), L-tyrosyl-leucine (Tyr-Leu), L-tyrosyl-L-
Isoleucine (Tyr-1ie), L-tyrosyl-L
-valine (Tyr-Val), tyrosyl-L-aspartic acid (Tyr-hesp), L-tyrosyl-
Lysine (Tyr-Lys), L-tyrosyl-L-threonine (Tyr-Thr), L-tyrosyl-L-glutamic acid (Tyr-Gtu), and Tyr-Tyrone-glutamine (Tyr-Glu) are used.
上記のチロシン残基を含むジペプチドの中から少なくと
も１種のジペプチドを配合することによって、高濃度の
Ｔｙｒを含有するアミノ酸栄養輸液組成物を提供する。By blending at least one dipeptide among the dipeptides containing tyrosine residues described above, an amino acid nutritional infusion composition containing a high concentration of Tyr is provided.
さらに 本発明に係るアミノ酸及びジペプチドは、ａ離
型のみならず薬理学的に許容される塩、例えばナトリウ
ム塩、カリウム塩等の金属塩、塩酸、硫酸等の鉱酸塩若
しくは酢酸塩、乳酸塩等の有機酸塩の形で使用すること
ができる。また、ジペプチドとした以外のアミノ酸は、
薬理学的に許容されるＮ−アシル誘導体やエステル誘導
体あるいはオリゴペプチドとして用いてもよい、また製
剤化する場合においては、通常用いられている安定剤や
ｐＨ調整剤等を使用し、公知の方法に従って製造できる
。Furthermore, the amino acids and dipeptides according to the present invention can be used not only as release agents but also as pharmacologically acceptable salts, such as metal salts such as sodium salts and potassium salts, mineral salts such as hydrochloric acid and sulfuric acid, acetate salts, and lactate salts. It can be used in the form of organic acid salts such as. In addition, amino acids other than dipeptides are
It may be used as a pharmacologically acceptable N-acyl derivative, ester derivative, or oligopeptide, and when formulated, it may be prepared using commonly used stabilizers, pH adjusters, etc., using known methods. can be manufactured according to
〔作 用］
チロシンをジペプチドとして用いたことから製剤学的な
制約を受けずに目的に合った濃度で処方を組むことがで
きた０本発明の処方、すなわち栄養輸液組成物は、病態
別アミノ酸輸液及び汎用性の高いアミノ酸輸液として、
各種疾患時に優れた栄養効果を発揮する。[Function] Because tyrosine is used as a dipeptide, it is possible to formulate a prescription at a concentration that suits the purpose without being subject to pharmaceutical restrictions. As an infusion and a highly versatile amino acid infusion,
It exhibits excellent nutritional effects in the treatment of various diseases.
なお、本発明に係るジペプチドは、生体に有効に利用さ
れる。Note that the dipeptide according to the present invention is effectively utilized in living organisms.
以下に、実施例と試験例を示し、本発明をより具体的に
説明する。EXAMPLES Below, the present invention will be explained in more detail with reference to Examples and Test Examples.
〔実施例１］
・表１に示したアミノ酸組成物にＴｙｒ−Ａｌａ ８
．６ ｇを加え、注射用蒸留水に加熱溶解し、全量を０
．９９１とした後、酢Ｍ溶液あるいは他の有機酸溶液（
乳酸、リンゴ酸、クエン酸など）でｐＨを６．０〜７．
０に調整した後、全量をＩＮとした。この水溶液を孔径
０．４５μのミリポアフィルタ−で濾過し、２００−の
ガラスバイアルに充填、窒素置換を行った後密栓した。[Example 1] Tyr-Ala 8 was added to the amino acid composition shown in Table 1.
．． Add 6 g, heat and dissolve in distilled water for injection, and reduce the total amount to 0.
．． 991, add vinegar M solution or other organic acid solution (
(lactic acid, malic acid, citric acid, etc.) to adjust the pH to 6.0-7.
After adjusting to 0, the entire amount was taken as IN. This aqueous solution was filtered through a Millipore filter with a pore size of 0.45 μm, filled into a 200-mm glass vial, replaced with nitrogen, and then sealed tightly.
これを高圧蒸気滅菌して静脈投与用輸液を調製した。こ
の製剤はジペプチドをＡｌａとＴｙｒに換算すると、そ
れぞれ３．０ｇノ！と６．２ｇ／Ｐ含むことになる。This was sterilized using high-pressure steam to prepare an infusion solution for intravenous administration. This preparation has a dipeptide of 3.0g each in terms of Ala and Tyr! and 6.2g/P.
表１ アミノ酸配合量（ｇ＃り
〔実施例２〕
表２に示したアミノ酸組成物にＬｅｕ−Ｔｙｒ ７．２
ｇを加え、以下実施例１と同様の方法に従って静脈投
与用輸液を調製した。この製剤はジペプチドをＬｅｕ
とＴｙｒに換算すると、それぞれ３．２ｇ＃！と４．４
ｇ／ｌ含むことになる。Table 1 Amino acid compounding amount (g# [Example 2]) Leu-Tyr 7.2 was added to the amino acid composition shown in Table 2.
g was added thereto, and an infusion solution for intravenous administration was prepared in the same manner as in Example 1. This formulation contains dipeptides with Leu
When converted to Tyr, it is 3.2g#! and 4.4
g/l will be included.
表２ アミノ酸配合！（ｇ＃り
〔実施例３〕
表３に示したアミノ酸組成物にシａｌ−Ｔｙｒ１１．８
ｇを加え、以下実施例１と同様の方法に従って静脈投
与用輸液を調製した。この製剤はジペプチドをＶａｌ
とＴｙｒに換算すると、それぞれ４．９ｇ／ｌと１．６
ｇ／ｌ含むことになる。Table 2 Amino acid combination! (Example 3) The amino acid composition shown in Table 3 was
g was added thereto, and an infusion solution for intravenous administration was prepared in the same manner as in Example 1. This formulation contains dipeptides with Val
and Tyr, respectively, 4.9g/l and 1.6
g/l will be included.
表３ アミノ酸配合量（ｇ／ｌ
実施例４〜１３
表４に示したアミノ酸組成物と各ペプチドを配合し、以
下実施例１と同様の方法に従って静脈投与用輸液を調製
した。Table 3 Amino acid blend amount (g/l) Examples 4 to 13 The amino acid composition shown in Table 4 and each peptide were blended, and an infusion solution for intravenous administration was prepared in the same manner as in Example 1.
表４−１ アミノ酸及びジペプチド配合ｆｆｉ（ｇ／
ｌ）（以下余白）
表４
アミノ酸及びジペプチド配合Ｎ（ｇ／ｌ）〔試験例１］
体重約１７０ ｇのＳＤ系雄性ラットに麻酔下、右上大
静脈にシリコンラバーカテーテルを留置し、直ちに高カ
ロリー輸液療法にて１週間輸液投与した。投与した栄養
輸液は、糖・電解質、ビタミン及び微量元素は、同一組
成でアミノ酸組成のみ異なる輸液とした。輸液は、実施
例１、対照輸液は表５に示した処方の輸液！、Ｉ＋を使
用した。Table 4-1 Amino acid and dipeptide combination ffi (g/
l) (blank below) Table 4 Amino acid and dipeptide combination N (g/l) [Test Example 1] A silicone rubber catheter was placed in the right superior vena cava under anesthesia in SD male rats weighing approximately 170 g, and immediately high-calorie injection was performed. Infusion therapy was administered for one week. The nutritional infusions administered had the same composition of sugars, electrolytes, vitamins, and trace elements, but differed only in amino acid composition. The infusion was the one shown in Example 1, and the control infusion was the one shown in Table 5! , I+ was used.
効果の検討は、体重変化及び窒素出納にて行った。その
結果、表６に示すように対照輸液に比較して明らかな改
善を６１認することができた。The effects were examined by examining body weight changes and nitrogen balance. As a result, as shown in Table 6, clear improvement was observed in 61 cases compared to the control infusion.
表５ 対照輸液！、ＩＩのアミノ酸組成表６
実施例１の栄養効果
試験例２〜５
実施例２，３，６．１３と表７に示した対照輸液を用い
て試験例１と同様の方法により実施した。その結果を表
８に示した。Table 5 Control infusion! , II Amino Acid Composition Table 6 Nutritional Effect Test Examples 2 to 5 of Example 1 Tests were carried out in the same manner as Test Example 1 using Examples 2, 3, 6.13 and the control infusion shown in Table 7. The results are shown in Table 8.
表７−１ 各試験例の対照輸液の組成（以下余白）
表７−２
各試験例の対照輸液の組成
表
実施例２〜５の栄養効果
［試験例６］
体重約１７０ｇのＳＤ系雄性ラット用い、麻酔下に一方
の腎臓の皮質部分を外科的に削除し、２週間後に他方の
腎臓を摘出した。腎臓摘出後２週間口に血中尿素窒素並
びにタレアナニン値を測定しその濃度が各々６０ ｍｇ
／ａ、 １ 、 ４ ｍｇ／ａ以上のものを腎臓病の
疾患モデルとした。このランドの右上大静脈にシリコン
ラバーカテーテルを留置し高カロリー輸液療法にて１週
間の輸液管理を行った。投与した栄養輸液は、糖・電解
質、ビタミン及び微量元素は同一組成で、アミノ＃ｉ組
成のみ異なる輸液とした。輸液は、実施例１と表５に示
した対照液１．１１を用いた。Table 7-1 Composition of control infusion for each test example (blank below) Table 7-2 Composition of control infusion for each test example Nutritional effects of Examples 2 to 5 [Test Example 6] SD male rats weighing approximately 170 g Using this method, the cortex of one kidney was surgically removed under anesthesia, and the other kidney was removed 2 weeks later. Two weeks after kidney removal, blood urea nitrogen and taleanine levels were measured and the concentrations were 60 mg each.
/a, 1, 4 mg/a or more was used as a kidney disease model. A silicone rubber catheter was placed in the right superior vena cava of this land, and fluid management was performed for one week using high-calorie fluid therapy. The nutritional infusions administered had the same composition of sugars/electrolytes, vitamins, and trace elements, but differed only in the amino #i composition. For the infusion, the control solution 1.11 shown in Example 1 and Table 5 was used.
その結果、表９に示す如く、実施例１の輸液は体重変化
、窒素出納において明らかな改善を確認することができ
た。As a result, as shown in Table 9, it was confirmed that the infusion of Example 1 clearly improved body weight change and nitrogen balance.
表９ 実施例１の栄養効果
（以下余白）
試験例７〜ｌＯ
実施例２，３，６．１３と表７に示した対照輸液を用い
て試験例６と同様の方法により実施した。その結果を表
１０に示した。Table 9 Nutritional effects of Example 1 (blank below) Test Examples 7 to 1O Tests were carried out in the same manner as Test Example 6 using Examples 2, 3, 6.13 and the control infusion shown in Table 7. The results are shown in Table 10.
表１０ 実施例２．３．６．１３の栄養効果（発明の
効果〕
本発明は、各種疾患時に優れた栄養効果を発揮するＬ−
チロシンのジペプチドを配合したアミノ酸組成物に関す
るもので、Ｌ−チロシンを製剤学的制約を受けることな
く高濃度化したアミノ酸輸液を提供することができる。Table 10 Nutritional effects of Example 2.3.6.13 (effects of the invention) The present invention provides L-
This invention relates to an amino acid composition containing a tyrosine dipeptide, and can provide an amino acid infusion with a high concentration of L-tyrosine without being subject to pharmaceutical restrictions.
特許出願人 森下製薬株式会社Patent applicant: Morishita Pharmaceutical Co., Ltd.
Claims (1)
含むジペプチドの少なくとも１種を配合した組成物であ
って、該ジペプチドをアミノ酸に換算したとき、少なく
とも下記アミノ酸を下記の組成範囲内で含有し、Ｌ−フ
ェニルアラニンに対するＬ−チロシンの重量比（Ｌ−チ
ロシン／Ｌ−フェニルアラニン）が０．１以上であり、
Ｌ−チロシンの濃度が０．６ｇ／ｌ以上であることを特
徴とする栄養輸液組成物。 ▲数式、化学式、表等があります▼[Scope of Claims] A composition containing at least one type of dipeptide containing an essential amino acid, a non-essential amino acid, and an L-tyrosine residue, wherein when the dipeptide is converted into an amino acid, at least the following amino acids are contained in the following composition. The weight ratio of L-tyrosine to L-phenylalanine (L-tyrosine/L-phenylalanine) is 0.1 or more,
A nutritional infusion composition characterized in that the concentration of L-tyrosine is 0.6 g/l or more. ▲Contains mathematical formulas, chemical formulas, tables, etc.▼
Priority Applications (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP63273826A JP2799178B2 (en) | 1988-10-28 | 1988-10-28 | Nutritional infusion composition containing L-tyrosine dipeptide |
| EP89111321A EP0347890B1 (en) | 1988-06-22 | 1989-06-21 | Amino acid nutrient compositions |
| US07/369,123 US5036052A (en) | 1988-06-22 | 1989-06-21 | Amino acid nutrient compositions |
| DE89111321T DE68905387T2 (en) | 1988-06-22 | 1989-06-21 | Amino acid food compositions. |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP63273826A JP2799178B2 (en) | 1988-10-28 | 1988-10-28 | Nutritional infusion composition containing L-tyrosine dipeptide |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH02121928A true JPH02121928A (en) | 1990-05-09 |
| JP2799178B2 JP2799178B2 (en) | 1998-09-17 |
Family
ID=17533091
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP63273826A Expired - Lifetime JP2799178B2 (en) | 1988-06-22 | 1988-10-28 | Nutritional infusion composition containing L-tyrosine dipeptide |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP2799178B2 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US11278586B2 (en) | 2017-09-25 | 2022-03-22 | Kao Corporation | Highly absorbable oral tyrosine formulation |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US11208467B2 (en) * | 2017-09-07 | 2021-12-28 | Daiichi Sankyo Company, Limited | Peptides inhibiting KLK1, KLK4, or KLK4 and KLK8 |
| AU2022316976A1 (en) * | 2021-07-27 | 2024-02-29 | Px Ing, Llc | Bioactive compositions and methods of use thereof |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS4862917A (en) * | 1971-12-09 | 1973-09-01 |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0347890B1 (en) | 1988-06-22 | 1993-03-17 | Roussel Morishita Co., Ltd. | Amino acid nutrient compositions |
-
1988
- 1988-10-28 JP JP63273826A patent/JP2799178B2/en not_active Expired - Lifetime
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS4862917A (en) * | 1971-12-09 | 1973-09-01 |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US11278586B2 (en) | 2017-09-25 | 2022-03-22 | Kao Corporation | Highly absorbable oral tyrosine formulation |
Also Published As
| Publication number | Publication date |
|---|---|
| JP2799178B2 (en) | 1998-09-17 |
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